1. Field of the Invention
The present invention relates to a peptide derivative, and to the use of the same.
2. Description of Related Art
Today, the estimated number of type-II diabetics in Japan exceeds 8,800,000 according to the statistic in fiscal 2007, and has been increasing further continuously, as compared with fiscal 2002. As a measure against this increase, interventions for preventing diabetes from developing have been made based on the glucose tolerance test, resulting, however, in unsatisfactory effects. The cause is as follows: at such a borderline stage that functional abnormalities are found by the glucose tolerance test, disorders of pancreatic islets have already advanced to a high degree, and this stage possibly is too late as a time for starting interventions.
Recently, it has been reported at home and overseas that even in type-II diabetics the amount of pancreatic islets already has decreased upon the development, and it has been considered that a further decrease in pancreatic β-cells after the development is one of the resistance factors against treatment for type-II diabetics. Therefore, if the amount of pancreatic islets and/or the amount of pancreatic β-cells is detected, there is possibility for the clarification of pathogenesis, the ultra-early diagnosis, and the prevention of development of type-I and type-II diabetes. For this purpose, molecular probes for imaging that allow determination of the amount of pancreatic islets and/or the amount of pancreatic β-cells have been researched and developed.
In designing a molecular probe for imaging, various target molecules in pancreatic cells, particularly functional proteins specific in the β-cells, are being researched. Among these, GLP-1R (glucagon-like peptide-1 receptor) is being researched as a target molecule; GLP-1R is distributed in pancreatic β-cells, and is a seven-transmembrane G protein coupled receptor.
As molecular probes for imaging that use GLP-1R as a target molecule, the following are researched: a peptide derivative of GLP-1 having a C-terminus to which a labeling molecule is bonded; a peptide derivative of exendin-3 having a C-terminus to which a labeling molecule is bonded; and a peptide derivative of exendin-4 having a C-terminus to which a labeling molecule is bonded (e.g., JP 2008-511557 A; M. Gotthardt et al., “A new technique for in vivo imaging of specific GLP-1 binding sites”: First results in small rodents, Regulatory Peptides 137 (2006) 162-267; and M. Beche et al., “Are radiolabeled GLP-1 receptor antagonists useful for scintigraphy?”: 2009 SNM Annual Meeting, abstract, Oral Presentations No. 327). In addition, a derivative of exendin (9-39) is proposed (e.g., WO 2010/032509; M. Beche et al., “Are radiolabeled GLP-1 receptor antagonists useful for scintigraphy?”: 2009 SNM Annual Meeting, abstract, Oral Presentations No. 327; and H. Kimura et al., Development of in vivo imaging agents targeting a glucagon-like peptide-1 receptor (GLP-1R) in pancreatic islets. 2009 SNM Annual Meeting, abstract, Oral Presentations No. 326).